PRELIMINARY CHEMICAL AND PHARMACOLOGICAL STUDY OF ASTRAGALUS SPINOSUS (Muschl) GROWN IN KUWAIT.
M.Th. Ghoneim, A.R. AlGindy, R. Alami, E. Shoukry and
Some preliminary pharmacological studies were carried out on the active ingredients and extracts obtained from Astragalus spinosus (Muschl). The glycoside was shown to possess postive intropic propeties as demonstrated from its effect on the isolated mammalian heart and rabbit atria. The alkaloidal fraction was found to produce a spasmolytic effect mostly probably through a direct action. The alkaloidal fraction showed moderate histamine and serotonin antagonizing effects. The alcoholic and cloriform extracts of the plant showed potent anti-spasmodic effect as shown from their effect on smooth muscles, this action of the root showed some histamine and serotonin antagonizing effects.
The alcoholic extract of the schools showed a similar effect to that produced by the glycoside. The chloroform extract of the shoots showed some antispasmodic effect in addition to some antihistaminic and anti-serotonin effect.
There are many species of Astragalus all over the world. The toxicity caused (1) by its ingestion by the live stock is divided into three groups (a) due to high percentage of selenium accumulated by the plant, (b) aliphatic nitro compounds, (c) chronic true "loco" symptoms appearing particularly in horses. Astragalus Spinosus (muschl) grows in Egypt and Kuwait. Khaphaga et al (2) found that it contains glycoside but nothing mentioned about itspharmacological action. So the aim of this work is: To study its chemical compositions and to screen it pharmacologically.
The glycoside produced only a slight inhibitory effect on the smooth muscles, no significant effect on the skeletal muscle. On the isolated perfused mammalian heart, the glycoside in a small concerntration produced a temporary depression followed by a gradual and slow stimulant effect mainly manifested on the amplitude of contraction. During the primary inhibtory phase, there was a slight decrease in the heart rate and coronary flow. With large doses, the primary inhibitory phase lasted for longer duration and was accompanied by a decrease in the heart rate which may be followed bycardiac arrhythmias and lastly cardiac standstill may occur. The stimulant effect of the glycoside was not abolished after Badrenergic receptors blockade with propranololo. Administration of the glycoside to hypodynamic heart (perfused with Ringer Licke containing 2.5-12 u.g. quinine Hel/ml) was found to decrease or prevent the induced hypodynamic state of the heart. On the isolated rabbit's atria, the glycoside produced a stimulant effect mainly on the amplitude of contraction. The effect was slow to start. The effect is not medicated through sympathetic stimulation. One toad's heart, the glycoside produced a stimulant effect mainly in the ampltude of contraction. No significant effect was observed on the bloodpressure of spinal cat. The alkaloidal fraction showed a mild inhibitory effect on rabbit jejunum. It reduced the response of the guinea pig to the effect of histamine, serotonin and angiotension but not to the effect of acetylcholine. The alkaloidal fraction decreased the response of rat fundus stomach to serotonin. The effect is dose-dependent. The response to angiotension was also decreased but after a large concentration of the alkaloid. The respoonse to acetylcholine was not affected. On guinea pig trachea, the alkaloidal fraction reduced the response to histamine. The effect is dose-dependent. On the rat uterus, the alka-loid produced a potent inhibitory effect on the response of the muscle to angiotenin. No effect was observed on the skeletal muscle. On the mammalian heart, the alkaloidal fraction produced a stimulant effect mainly in the amplitude of contraction. The stimulation was not medi-ated through sympathetic stimulation. The alcoholic extract of the shoots showed similar effects to those produced by the glycoside. The chloroform extract of the shoot demonstrated effects more or less similar to those produced by the alkaloidal fraction. The alcoholic extract of the roots shwoed an inhibitory effect on the smooth muscles. The extract of the shoot demonstrated effects more or less similar to those produced by the alkaloidal fraction. The alcoholic extract of the root swheod an inhibitory effect on the smooth muscles. The extract inhibited the tone and rhythmic activity of the rabbit duodenum and jejunum, the effect is dose-dependent and th emuscles regained normal activity after washing of the drug. No siginificant effect was observed on the response of the muscle to acetyl choline, but the extract reduced the response to Serotonin and abolished the response to barium chloride.
On the guinea pig ileum, the extract inhibited the response of the muscle to contractions induced by histamine, Serotonin and angio-tensin. The response to nicotine is not affected except in very large conentration of the extract. The effect of the extract is dose-dependent and reversible. On the rat stomach fundus strip, the extract reduced the response to serotonin. On the isolated guinea pig tracheal strip, the extract inhibited the response to angiotensin but not to histamine. On the isolated rabbit aortic strip, the extract reduced the response of the muscle to angiotension but not to noradrenaline. On the mammalian heart, the extract produced a direct stimulant effect. The chloroform extract of the roots was found to produce similar effect except that most of the effects produced on the smooth muscles were mediated through a direct inhibitory effect, where the extract was able to decrease the response os smooth muscles tested angiotensin and barium chloride.
Some pharmacological actions of the ingredients separated from astragalus, in addition to the extracts have been investigated. The glycoside is suggested to possess a positive inotropic effect on the heart as shown frim its effect on the isolated mammalian heart. This preparation is sensitive to trace a cardiac glucoside like activity (Brown et al, 1962 14, HOlland and Briggs, 1964 15. The inotropic effect of the glycoside was manifested on both normal and hypodynamic hearts. It was reported that the degree of positive inotropic effect depends, to a great extend, on the functional state of the cardiac muscle (sciarine et al 1943 16, Braunwald et al, 1961 17, Rodman and Pastor, 1963 18 where the effect is more pronounced on hypodynamic heart than in sufficient one. High concentrations of the gycoside were found to produced cardiac inhibition with a decrease in the heart rate, arrhythmias may occur and then cardiac standstill. High concentrations of substances with cardiac glycoside like activity are known to impair the cardiacc contractibility, produce contracture in isolated hearts, the heart rate may be reduced and arrhythmias are likely to occur and finally the heart functionally arrested (Klaus, 1966 19. The glycoside was also shown to exert a positive inotropic effect on the isolated atria. Corresponding experiments for testing cardiac glycosidelike activity were reported to be performed on isolated mammalian atria (Ehmer et al, 1964 20, Erjarec & Adamic, 1965 21, Greef et at 1965 22. The inotropic effect of the glycoside was not mediated through an adrenergic mechanism, most probably, it is mediated through a direct effected on the myocardium. Therapeutic actions of cardiac glycoside-like activity on the cardiac muscle are not mediated thorugh adrenergic mechanisms and are not abolished by reserpine or adrenergic B-receptor blockers (Moran & Perkins, 1958 23, Morrow et al, 19673 24, Forster & Stolzenberg, 1963 25. The glycoside is nearly devoid of significant antispasmodic effects.
The alkaloidal fraction produced an inhibitory effect on the smooth muscles. The ability of the alkaloidal fraction to inhibit the response to angiotensin indicates that it has a direct spasmolytic effect. In addition, the alkaloidal fraction showed moderate histamine and serotonin anto-gonizing effects. No significant anticholinergic effect was observed. The alkaloidal fraction showed a mild direct stimulant effect on the heart. The alcoholic and chloroform extract of the roots of astagalus showed potent anti-spasmodic effect. The effect isi not mediated through an anticholineragic effect. It is suggested that this effect is mediated througha direct action on the smooth muscles as proved from their antagonistic action to the spasmogenic effect of either angiotensin or barium chloride. The alcoholic extract showed some histamine and serotonin antogonizing effects. The alcoholic extract of the shoots of astragalus showed a similar effect to that of the glycoside indicating that the glycoside is the main active principle present in this extract. The chloroform extract of the shoots of astragalus also produced similar affects to those shown by the alkaloidal fraction suggesting that the alkaloid may constitute its main active ingredient.
Astragalus contains some active ingredients having different pharmacological effects. The main action of the glycoside and the alchoholic extract of the shoot was a direct cardiac stimulant effect. The other fractions showed potent antispasmodic effect. This is a preliminary study. Now, work is in progress to determine the other possible pharmacologbical effects and toxicity of the plant.